The atomic force microscope (AFM) is an ultra-sensitive force transduction instrument capable of detecting force interactions between materials, molecules and chemical groups. Molecular force detection has application in biomedical diagnostics, drug development, genome analyses, and many other areas. Key to the implementation of molecular force detection int he commercial environment is the development of robust reliable modification AFM tips. Since specificity and sensitivity is dependent upon tip/sample contact area, it is critical to have access to the full spectrum of tip sizes for each molecular force detection application. In this proposal we will test a new method for the modification of AFM tips with functionalized microparticiles in a size range that fill s an existing void in modified tip sizes ( about 200nm to e(mu) in diameter). The method to be tested uses a near infrared diode laser to manipulate microparticles (in conjunction with mechanical manipulation) and locally "weld" them to AFM tips. Advantages of this approach include: tip modification in physiological solution, production of small diameter tips with define chemical and/or biological function, increased throughput, improved quality control, and ready development of semi-automated tip manufacture processess. PROPOSED COMMERCIAL APPLICATIONS: Discovery and diagnostics of interactions between materials, chemical groups and biological molecules. Application include new drug discovery, genome mapping and manipulation, immunoassays, protein/nucleic acid interactions, receptor/ligand interactions.